This invention relates to a device for detecting a trace amount of substance, particularly to a material recognizing device for detecting a bio-molecular or other organic material or the like with a high sensitivity and on a real time basis.
A biosensor system as a means to monitor a biological function instantaneously has been intensively studied and developed for practical applications heretofore. The basic composition of a biosensor consists of a section for detecting a biological substance and a section for transducing a signal. A biological substance is complexed with the recognizing component of the biosensor, and ensures an ability to detect a bio-molecule, while the signal transducing section transduces a change obtained through the detection of a biological substance into an electric signal. There are many kinds of biological substances which can be detected on the basis of their molecular properties, and they include enzymes, antibodies, binding proteins, lectin, receptors, etc. Examples of biological substances include those that have a molecule recognizing ability and/or catalyzing function. They include enzymes, complex enzyme systems, intracellular organelles, microorganisms, animal cells, plant cells, etc. The catalytic activity of these substances depends on the structure characteristic with enzymes, and can be approximated, in its essence, by the kinetic equation by Michaelis and Menten. Other examples include substances that have a molecule recognizing function, and which forms a stable complex through a biological affinity. They include antibodies, lectin, binding proteins, receptors, etc. The basic designing of a bio-sensor proceeds with attention paid to the above properties. With the recent development of biotechnology, the range of biological substances available for the biosensor has been widened, and thus thermo-resistive enzymes, monoclonal antibodies or the like have come have to be available. To convert the data obtained through molecule recognition into electric signals, physical parameter converting elements such as electrochemical reactions, and an FET, thermistor, piezoelectric element, surface elastic wave element, photodiode, etc. have been utilized.
However, the above-described conventional biosensor devices have technical problems as described below. Firstly, the method for producing a thin film for molecular recognition includes methods based on photoresistance, electrochemical polymerization, manufacture of an LB film, etc. The method based on photoresistance consists of forming a photoresistant film on the entire surface of an ISFET (ion sensitive field effect transistor), exposing only gate parts by lithography, and forming a highly affinitive molecule recognizing film (organic film or biomolecular film) on a gate insulating film. Then, the photoresistant layer is peeled off to leave the molecule recognizing film bonded to gate parts, which serves as a sensor. With this method, however, it is difficult to neatly prepare minute dot electrodes on the molecule recognizing film, and thus an incompletely finished edge of dots results. A reduced yield occurs. Further, waste of materials occurs as a result of lithography. Namely, 99% of photo-setting resin is discarded without being incorporated into actual products, that is, the method causes a wasteful consumption of resources on earth, and contamination of natural environments. This is a big problem. LB technique (Langmuir-Blodgett""s technique) is a method whereby a mono-molecular film is formed on the surface of water, and the film is transferred onto the surface of a solid substrate, and for the method to be effective, it is necessary for the mono-molecular layer to have a structure comprising hydrophobic and hydrophilic sections in a balanced state. This method, however, is problematic in that the quality of LB film produced thereby is unsatisfactory in reliability: The film has immeasurable flaws or pores thereupon, and does not allow the formation of an uniform molecular film. Accordingly, with the product manufactured by this method, it is difficult to distinguish a change detected by a molecule recognizing film formed on an electrode from a local change of the electrode.
Furthermore, the sensor film prepared by these methods is a molecule recognizing film composed of one kind of molecule, which recognizes only one kind of biological substance to which the film is sensitive. Still further, it is impossible with these methods to apply different biological substances simultaneously to a plurality of electrodes. Thus, they are problematic in operability and detection efficiency.
With a view to cope with above-described inconveniences, this invention aims at introducing a method for producing a molecule recognizing film distinct from the conventional ones, and further to introduce a method being different, in the manner of detecting biological substances, from the conventional ones.
Namely, one object of this invention is to provide a method for forming, distinct from conventional methods, a molecule recognizing film, uniform and high in quality on a sensor electrode efficiently and in a short time. Further, another object of this invention is to provide a method for forming a plurality of minute sensor electrode dots by said new method for preparing a molecule recognizing film, and for accurately applying a great number of biological samples to be evaluated onto said plural minute sensor electrode dots in a short time and efficiently.
According to one aspect of this invention, with a sensor device comprising organic thin films formed on an arbitrarily chosen electrode board circuit and electrodes, and a transducing element to transduce information obtained by the organic thin films into electric signals, provided is a method for producing the sensor device wherein a solution of a material of the thin film is accurately printed via an ink-jet nozzle as micro-dots onto the required surface of microelectrodes so that the organic thin films are formed on the electrodes, thereby realizing highly dense microelectrodes.
According to this invention, provided is the sensor device wherein the solution of a material of the thin film comprises an electro-conductive polymer dissolved in a solvent.
According to this invention, provided is the sensor device wherein the solution of a material of the thin film comprises a solution of a silicone-based surface modifying agent, or a mixture thereof with a solvent.
According to this invention, provided is the sensor device wherein the solution of a material of the thin film comprises a mixture resulting from dissolution of a thiol compound in a solvent, and gold thin films are formed on the surface of the electrodes.
According to another aspect of this invention, with said sensor device, provided is a method for evaluating a trace amount of liquid wherein a solution of a sample substance to be sensed is ejected into air as micro-dots via an ink-jet nozzle to fall on the surface of organic thin films of microelectrodes so that the substance is submitted to evaluation.
According to this invention, with the sensor device, provided is a method for evaluating a trace amount of liquid wherein the solution or liquid substance to be sensed and ejected into air as micro-dots via the ink-jet nozzle comprises a protein, DNA, antibody, receptor, lectin, a bio-molecule from an animal or plant cell, or a physiologically active substance, or an aqueous solution thereof.
According to another aspect of this invention, provided are the sensor device and the method for evaluating the function of a liquid wherein the electrode or electric circuit is formed on a plastic substrate.
According to another aspect of this invention, provided are the sensor device and the method for evaluating the function of a liquid based on the use of the sensor device wherein the electric circuit is composed of poly-silicon thin film transistors.